Potential subtype-specific therapeutic approaches in small cell lung cancer.

Abstract

Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients. Substantial research on the biological and molecular heterogeneity of SCLC has been conducted in the last years. Recent results from comprehensive profiling studies have shown that unique major SCLC subtypes can be distinguished based on the relative expression of key transcription regulators (ASCL1, NEUROD1, POU2F3) or distinct inflammatory features. Understanding the differing molecular characteristics of these distinct subtypes has resulted in the identification of specific therapeutic vulnerabilities. The recently introduced molecular SCLC subtype classification represents a substantial progress towards a personalized and more efficacious approach in SCLC. The consequences of this paradigm shift provide hope for improved patient care and clinical outcomes in this exceptionally lethal thoracic malignancy.